Although there is compelling evidence to support the view that altered endocytic-lysosomal functions of synovial tissue may play a role in the joint tissue injury seen in rheumatoid arthritis (RA), there are no data to quantitate these functions in human synovial cells. In these studies we propose to investigate the intrinsic ability of synovial tissue cells in monolayer culture to take up and digest both simple proteins and particulate or soluble immune complexes. We will compare these functions in synovial cells from patients with RA to cells from patients without disease or with other joint diseases. A careful analysis of the metabolic requirements and effects of known stimulators and inhibitors of endocytosis and intracellular digestion will clearly define any differences between these functions in the cells from patients with different disease states. Determination of the intra- and extra-cellular distribution of lysosomal enzymes, cyclic nucleotides and prostaglandins during uptake and digestion of soluble and particulate immune complexes by synovial cells will further delineate the possible contributions of these molecules to the mediation and modulation of tissue injury in RA. In addition, the interaction of extrinsically imposed joint and serous components such as hyaluronic acid, immunoglobulins, rheumatoid factors, prostaglandins and cyclic nucleotides with the endocytic-lysosomal activities of synovial cells will add to our understanding of their possible interactions and contributions in vivo to the disease state. Identical studies to those with synovial cells will be performed using cultured human peripheral blood monocytes from controls and individuals with RA. These additional experiments will serve as controls for the specificity of the synovial cell studies and may give us a better understanding of the functions of the endocytic-lysosomal apparatus of the monocyte in RA.